Why biofilm bacteria tolerate antibiotics
An established biofilm (bacteria stuck to a surface in a slimy matrix) lets bacteria survive antibiotics through slow growth and reduced drug entry, which need not involve a new mutation.
Remember
Slow-growing cells in an established biofilm survive antibiotics that work best on actively growing bacteria, so this survival (tolerance) comes from the cells' state and need not involve a new mutation.
Memory aid
free-living bacteria swim and divide, biofilm bacteria stick and slow down
Use it to recall the direction of the change: attached bacteria move less and divide less, which makes antibiotics that need active growth less effective.
A biofilm is a community of bacteria stuck to a surface and embedded in a slimy matrix that they make themselves. Bacteria living on their own are called planktonic (free-living, individual cells). After attaching, they multiply and produce the extracellular matrix, a scaffold secreted outside the cells and made mainly of proteins, nucleic acids, lipids and polysaccharides (long chains of sugars).
The matrix holds the community together, but it is not a sealed coat. Nutrients and chemical signals pass through it, yet conditions differ from place to place inside it, so cells in nutrient-poor regions grow slowly.
The bacteria also signal to each other. Each cell releases a small signalling molecule called an autoinducer, and when enough cells are present the signal reaches a critical level. This is quorum sensing: the bacteria detect how crowded they are. In a biofilm the signals help to switch cells to a slower metabolism and to stop dividing.
Many antibiotics work best on actively growing bacteria, so slow-growing cells are killed poorly. The matrix can also reduce how much of some drugs gets in, but this only partly explains the tolerance. The result is tolerance: survival of treatment because of the cells' state and surroundings, not because of a newly acquired resistance mutation. A resistance mutation changes individual bacteria and gives permanent resistance, so it would be expected to show up on laboratory testing. A biofilm organism can therefore test as susceptible (the bacteria grown freely in a dish respond to the antibiotics) and still survive in the patient.
Biofilms form on living and non-living surfaces, including devices such as catheters and joint replacements. Removing the infected device, as well as giving antibiotics, may be part of treatment.
Key facts
- Biofilm
- bacteria attached to a surface and held in a slimy matrix of their own making.
- Matrix
- a scaffold made mainly of polysaccharides (long chains of sugars), proteins, nucleic acids and lipids that holds the community together; it lets nutrients and signals through, so it is not a sealed coat.
- Signalling
- autoinducers pass between the cells and help to switch them to a slower metabolism and to stop dividing.
- Slow growth
- antibiotics that work best on actively growing cells kill slow-growing or non-growing cells poorly.
- Tolerance
- survival of treatment because of the cells' state, which can be lost when the bacteria leave the biofilm, rather than an inherited resistance gene.
- Clinical point
- an organism growing in a biofilm can test as susceptible in the laboratory and still survive antibiotics in the patient, particularly on a device such as a catheter.
Exam traps
- Fast replication is not what makes biofilms hard to treat, because bacteria deep in a biofilm usually grow and divide slowly, and slow growth makes many antibiotics less effective.
- Living tissue is not required for tolerance, because biofilms also form on non-living surfaces such as catheters.
- Flagella (the structures that drive swimming) matter in the free-swimming stage: bacteria in a biofilm change from a swimming state to a sticking state, so swimming away from the drug is not how they tolerate it.
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